In connection with recent hypotheses concerning carcinogenic mechanisms at the level of the genome, it has been suggested that certain chromosomal translocations frequently observed in human lymphoid neoplasms may involve immunoglobulin genes, and bring transcriptionally active portions of these genes into juxtaposition with other segments of the genome (oncogenes?), leading to their activation, and neoplastic transformation. This project will examine immunoglobulin gene involvement in translocations in both lymphoid and non-lymphoid human leukemias and lymphomas, and look for effects on adjacent gene segments. We will use a combination of cytogenetic methods (trypsin-Giemsa and G-11 banding, in situ hybridization) and appropriate DNA probes with Southern blotting techniques to determine, with fresh cells from patients and established cell lines, if in the chromosome translocations in human lymphoid tumors, which involve the long arm of chromosome 14 (14q), the short arm of chromosome 2 (2p), and the long arm of chromosome 22 (22q), the breakpoints in the chromosomes are within the immunoglobulin heavy and light chain genes located on these chromosome segments. Similar questions will be asked of relevant translocations observed in non-lymphoid hematopoietic tumors (e.g., the 9;22 translocation in chronic granulocytic leukemia). We will also determine the structural and functional status of Ig genes in these translocations, as well as the possible involvement of DNA sequences analogous to known viral onc-genes (e.g., c-myc, c-sis). Efforts also will be made to characterize and clone sequences involved in these translocations to determine their activity in the original tumor cells and their ability to function as "oncogenes" in transfection experiments. These studies should begin to test the intriguing hypothesis that translocation of segments of Ig genes is an important mechanism in human leukemogenesis, and perhaps provide clues as to how such effects are mediated.